Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

Verbal fluency is widely used as a clinical test but its utility in differentiating between neurodegenerative dementias and progressive aphasias, and from healthy controls, remains unclear. We assessed whether various measures of fluency performance could differentiate between Alzheimer’s disease, behavioural variant of frontotemporal dementia, non-fluent and semantic variants of primary progressive aphasia, progressive supranuclear palsy, corticobasal syndrome, and healthy controls. Category and letter fluency tasks were administered to 33 controls and 139 patients at their baseline clinical visit. We assessed group differences for total number of words produced, psycholinguistic word properties, and associations between production order and exemplar psycholinguistic properties. Receiver Operating Characteristic curves determined which measure could best discriminate patient groups and controls. Total word count distinguished controls from all patient groups, but neither this measure nor the word properties differentiated the patient groups. Receiver Operating Characteristic curves revealed that, when comparing controls to patients, the strongest discriminators were total word count followed by word frequency. Word frequency was the strongest discriminator for semantic variant of primary progressive aphasia versus other groups. Fluency word counts were associated with global severity as measured by Addenbrooke’s Cognitive Examination-Revised. Verbal fluency is an efficient test for assessing global brain-cognitive health but has limited utility in differentiating between cognitively- and anatomically-disparate patient groups. This outcome is consistent with the fact that verbal fluency requires many different aspects of higher cognition and language.

Objective: Verbal fluency is clinically widely used but its utility in differentiating between neurodegenerative dementias and progressive aphasias, and from healthy controls, remains unclear. We assessed whether the total number of words produced, their psycholinguistic properties, and production order effects could differentiate between Alzheimer's disease (AD), behavioural variant of frontotemporal dementia (bvFTD), non-fluent and semantic variants of primary progressive aphasia (PPA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and healthy controls. Methods: Category and letter fluency tasks were administered to 33 controls and 139 patients at their baseline clinical visit: 18 AD, 16 bvFTD, 26 nfvPPA, 26 svPPA, 36 PSP, and 17 CBS. We assessed group differences for total words, psycholinguistic word properties, and associations between production order and exemplar psycholinguistic properties. Receiver Operating Characteristic (ROC) curves determined which measure could best discriminate patient groups and controls. Results: Total word count distinguished controls from all patient groups, but neither this measure nor the word properties differentiated the patient groups. ROC curves revealed that, when comparing controls to patients, the strongest discriminators were total word count followed by word frequency. Word frequency was the strongest discriminator for svPPA versus other groups. Fluency word counts were associated with global severity as measured by Addenbrooke's Cognitive Examination-Revised (ACE-R). Conclusions: Verbal fluency is an efficient test for assessing global brain-cognitive health but has limited utility in differentiating between cognitively- and anatomically-disparate patient groups. This outcome is consistent with the fact that verbal fluency requires many different aspects of higher cognition and language.